The current method for treating a child's permanent tooth with an incompletely developed root and a necrotic root canal system is fraught with difficulty. Not only is the root canal system often difficult to fully disinfect, but the thin dentinal walls increase the risk of a subsequent root fracture, which often necessitates extraction of the tooth. Although this may occur in all children (eg., trauma), children from families with health care disparities are at particular risk due to a greater prevalence of caries. The current standard method of treating these cases is apexification (formation/induction of a calcified barrier across the root apex), which leaves a greatly weakened tooth with a poor long term prognosis. A recently reported regenerative procedure is a plausible treatment alternative. It involves the chemical disinfection of the root canal system followed by evoked bleeding into the root canal system, formation of a blood clot and immediate coronal seal. Built upon the concepts of tissue engineering, this new approach takes advantage of a rich supply of mesenchymal stem cells, possibly including the population of stem cells of the apical papilla (SCAP) that is adjacent to the open apex of the incompletely developed tooth. The objective of this R34 grant application is to plan and develop a subsequent U01 clinical trial protocol application that will test the central hypothesis that a regenerative clinical protocol, that involves the use of a triple antibiotic paste and evoked bleeding into the root canal system, will produce significantly greater continued development of dentinal wall thickness as compared to standard treatment (MTA apexification). This will be a prospective, Phase III, randomized, multi-center (3 sites: UTHSCSA, UCSF, UNC) controlled clinical trial. In the present R34 planning period, we will accomplish the following aims: Specific Aim 1: Develop a comprehensive clinical trial protocol that includes specified recruitment strategies and associated documents such as a Manual of Procedures, IRB protocol, consent form, clinical investigator's brochure, training manual, and proposed budget (for the U01 application). Specific Aim 2: Train and calibrate the research team for standardization of protocol procedures and data collection. Specific Aim 3: Develop tools and protocols required for data management, and appropriate and effective safety and operational oversight of the research. PUBLIC HEALTH RELEVANCE: This project is relevant to public health since children from families with health care disparities often have a greater risk of losing their permanent teeth due to caries or other factors. By studying a new and biologically-based method for treating infection and allowing the tooth to continue its development, this project directly addresses a key issue of high relevance to public health.